Dual Effects of β₃ Integrin Subunit Expression on Human Pancreatic Cancer Models

Abstract

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.

Methods: In view of these findings, we examined the role of β₃ in pancreatic cancer by generating two stable β₃-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.

Results: Transduction of β₃ selectively augmented the functional membrane αvβ₃ integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected in β₃-overexpressing cells. Moreover, tumors expressing β₃ displayed reduced growth. Interestingly, treatment of mice with an αv-blocking antibody inhibited the growth of β₃-expressing tumors to a higher extent.

Conclusion: Our results collectively support the hypothesis that αvβ₃ integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.